Vitamin D directly inhibits key phenotypic features of cardiac hypertrophy raising the possibility that it may function in an autocrine or paracrine fashion to suppress hypertrophy. However, for this hypothesis to be valid requires that cardiac cells possess the ability to regulate and respond to the active form of vitamin D. The components of the vitamin D system, specifically the VDR, 1 alpha-hydroxylase and 24-hydroxylase, will be examined and the response to hypertrophic stimuli characterized. The importance of vitamin D in cardiovascular function is supported by studies of the vitamin D receptor (VDR) knockout mouse, which develops cardiac hypertrophy. However, the underlying mechanisms involved are difficult to interpret given the pleiotropic effect of vitamin D. To determine the direct effects of endogenous vitamin D on the myocyte will require a tissue specific model, and so a cardiac-selective deletion of the murine VDR gene will be created and the response to a hypertrophic stimulus will be assessed in vivo. ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32HL086158-01
Application #
7156366
Study Section
Special Emphasis Panel (ZRG1-F10-H (20))
Program Officer
Meadows, Tawanna
Project Start
2007-02-01
Project End
2009-01-31
Budget Start
2007-02-01
Budget End
2008-01-31
Support Year
1
Fiscal Year
2006
Total Cost
$53,992
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Ni, Wei; Glenn, Denis J; Gardner, David G (2016) Tie-2Cre mediated deletion of the vitamin D receptor gene leads to improved skeletal muscle insulin sensitivity and glucose tolerance. J Steroid Biochem Mol Biol 164:281-286
Glenn, Denis J; Cardema, Michelle C; Ni, Wei et al. (2015) Cardiac steatosis potentiates angiotensin II effects in the heart. Am J Physiol Heart Circ Physiol 308:H339-50
Ni, Wei; Watts, Stephanie W; Ng, Michael et al. (2014) Elimination of vitamin D receptor in vascular endothelial cells alters vascular function. Hypertension 64:1290-8
Gardner, David G; Chen, Songcang; Glenn, Denis J (2013) Vitamin D and the heart. Am J Physiol Regul Integr Comp Physiol 305:R969-77
Glenn, Denis J; Wang, Feng; Nishimoto, Minobu et al. (2011) A murine model of isolated cardiac steatosis leads to cardiomyopathy. Hypertension 57:216-22
Glenn, Denis J; Wang, Feng; Chen, Songcang et al. (2009) Endothelin-stimulated human B-type natriuretic peptide gene expression is mediated by Yin Yang 1 in association with histone deacetylase 2. Hypertension 53:549-55
Glenn, Denis J; Rahmutula, Dolkun; Nishimoto, Minobu et al. (2009) Atrial natriuretic peptide suppresses endothelin gene expression and proliferation in cardiac fibroblasts through a GATA4-dependent mechanism. Cardiovasc Res 84:209-17
Chen, Songcang; Glenn, Denis J; Ni, Wei et al. (2008) Expression of the vitamin d receptor is increased in the hypertrophic heart. Hypertension 52:1106-12
Glenn, Denis J; Gardner, David G (2007) Lipids and the heart: neither feast nor famine. Hypertension 50:463-4